Pseudobulbar affect: No laughing matter

Pathological laughter and crying— pseudobulbar affect (PBA)—is a disor­der of emotional expression character­ized by uncontrollable outbursts of laughter or crying without an environmental trigger. Persons with PBA are at an increased risk of depressive and anxiety symptoms associated with an inappropriate outburst of emotion¹; such emotional acts might be incongruent with their underlying emotional state.

When should you consider PBA?
Consider PBA in patients with new-onset emotional lability in the presence of certain neurologic conditions. PBA is most common in patients with amyotrophic lateral sclerosis and stroke, in which an incidence of >50% has been estimated.² Other conditions asso­ciated with PBA include Parkinson’s disease, multiple sclerosis, frontotemporal dementia, traumatic brain injury, Alzheimer’s disease, epilepsy, normal pressure hydrocephalus, progressive supranuclear palsy, Wilson dis­ease, and neurosyphilis.³

Avoid PBA misdiagnosis
Depression is the most common PBA mis­diagnosis (Table). However, many clinical features distinguish PBA episodes from de­pressive symptoms; the most prominent dif­ference is duration. Depressive symptoms, including depressed mood, typically last weeks to months, but a PBA episode lasts seconds or minutes. In addition, crying, as a symptom of PBA, might be unrelated or ex­aggerated relative to the patient’s mood, but crying is congruent with subjective mood in depression. Other symptoms of depres­sion—fatigue, anorexia, insomnia, anhedo­nia, and feelings of hopelessness and guilt— are not associated with pseudobulbar affect.

PBA also can be differentiated from bi­polar disorder (BD) with rapid cycling or mixed mood episodes because of PBA’s relatively brief duration of laughing or cry­ing episodes—with no mood disturbance between episodes—compared with the sustained changes in mood, cognition, and behavior seen in BD.

Options for treating PBA
Serotonergic therapies, such as amitriptyline and fluoxetine, may exert effects by increas­ing serotonin in the synapse; dextrometho­rphan may act via antiglutamatergic effects at N-methyl-d-aspartate receptors and sig­ma-1 receptors.⁴ Dextromethorphan bind­ing is most prominent in the brainstem and cerebellum, brain areas known to be rich in sigma-1 receptors and key sites implicated in the pathophysiology of PBA. Although the precise mechanisms by which dextro­methorphan ameliorates PBA are unknown, modulation of excessive glutamatergic trans­mission within corticopontine-cerebellar circuits may contribute to its benefits.

Disclosure
The author reports no financial relationships with any company whose products are mentioned in this article or with manufacturers of competing products.

Pathological laughter and crying— pseudobulbar affect (PBA)—is a disor­der of emotional expression character­ized by uncontrollable outbursts of laughter or crying without an environmental trigger. Persons with PBA are at an increased risk of depressive and anxiety symptoms associated with an inappropriate outburst of emotion¹; such emotional acts might be incongruent with their underlying emotional state.

When should you consider PBA?
Consider PBA in patients with new-onset emotional lability in the presence of certain neurologic conditions. PBA is most common in patients with amyotrophic lateral sclerosis and stroke, in which an incidence of >50% has been estimated.² Other conditions asso­ciated with PBA include Parkinson’s disease, multiple sclerosis, frontotemporal dementia, traumatic brain injury, Alzheimer’s disease, epilepsy, normal pressure hydrocephalus, progressive supranuclear palsy, Wilson dis­ease, and neurosyphilis.³

Avoid PBA misdiagnosis
Depression is the most common PBA mis­diagnosis (Table). However, many clinical features distinguish PBA episodes from de­pressive symptoms; the most prominent dif­ference is duration. Depressive symptoms, including depressed mood, typically last weeks to months, but a PBA episode lasts seconds or minutes. In addition, crying, as a symptom of PBA, might be unrelated or ex­aggerated relative to the patient’s mood, but crying is congruent with subjective mood in depression. Other symptoms of depres­sion—fatigue, anorexia, insomnia, anhedo­nia, and feelings of hopelessness and guilt— are not associated with pseudobulbar affect.

PBA also can be differentiated from bi­polar disorder (BD) with rapid cycling or mixed mood episodes because of PBA’s relatively brief duration of laughing or cry­ing episodes—with no mood disturbance between episodes—compared with the sustained changes in mood, cognition, and behavior seen in BD.

Options for treating PBA
Serotonergic therapies, such as amitriptyline and fluoxetine, may exert effects by increas­ing serotonin in the synapse; dextrometho­rphan may act via antiglutamatergic effects at N-methyl-d-aspartate receptors and sig­ma-1 receptors.⁴ Dextromethorphan bind­ing is most prominent in the brainstem and cerebellum, brain areas known to be rich in sigma-1 receptors and key sites implicated in the pathophysiology of PBA. Although the precise mechanisms by which dextro­methorphan ameliorates PBA are unknown, modulation of excessive glutamatergic trans­mission within corticopontine-cerebellar circuits may contribute to its benefits.

Disclosure
The author reports no financial relationships with any company whose products are mentioned in this article or with manufacturers of competing products.

Pathological laughter and crying— pseudobulbar affect (PBA)—is a disor­der of emotional expression character­ized by uncontrollable outbursts of laughter or crying without an environmental trigger. Persons with PBA are at an increased risk of depressive and anxiety symptoms associated with an inappropriate outburst of emotion¹; such emotional acts might be incongruent with their underlying emotional state.

When should you consider PBA?
Consider PBA in patients with new-onset emotional lability in the presence of certain neurologic conditions. PBA is most common in patients with amyotrophic lateral sclerosis and stroke, in which an incidence of >50% has been estimated.² Other conditions asso­ciated with PBA include Parkinson’s disease, multiple sclerosis, frontotemporal dementia, traumatic brain injury, Alzheimer’s disease, epilepsy, normal pressure hydrocephalus, progressive supranuclear palsy, Wilson dis­ease, and neurosyphilis.³

Avoid PBA misdiagnosis
Depression is the most common PBA mis­diagnosis (Table). However, many clinical features distinguish PBA episodes from de­pressive symptoms; the most prominent dif­ference is duration. Depressive symptoms, including depressed mood, typically last weeks to months, but a PBA episode lasts seconds or minutes. In addition, crying, as a symptom of PBA, might be unrelated or ex­aggerated relative to the patient’s mood, but crying is congruent with subjective mood in depression. Other symptoms of depres­sion—fatigue, anorexia, insomnia, anhedo­nia, and feelings of hopelessness and guilt— are not associated with pseudobulbar affect.

PBA also can be differentiated from bi­polar disorder (BD) with rapid cycling or mixed mood episodes because of PBA’s relatively brief duration of laughing or cry­ing episodes—with no mood disturbance between episodes—compared with the sustained changes in mood, cognition, and behavior seen in BD.

Options for treating PBA
Serotonergic therapies, such as amitriptyline and fluoxetine, may exert effects by increas­ing serotonin in the synapse; dextrometho­rphan may act via antiglutamatergic effects at N-methyl-d-aspartate receptors and sig­ma-1 receptors.⁴ Dextromethorphan bind­ing is most prominent in the brainstem and cerebellum, brain areas known to be rich in sigma-1 receptors and key sites implicated in the pathophysiology of PBA. Although the precise mechanisms by which dextro­methorphan ameliorates PBA are unknown, modulation of excessive glutamatergic trans­mission within corticopontine-cerebellar circuits may contribute to its benefits.

Disclosure
The author reports no financial relationships with any company whose products are mentioned in this article or with manufacturers of competing products.